Evolutionary dynamics of recurrent hepatocellular carcinoma under divergent immune selection pressures.

ABSTRACT: Hepatocellular carcinoma (HCC) is a highly lethal, aggressive malignancy. Little is known about the evolutionary trajectories of HCC and how clinical decision-making could be informed based on biopsies of the initial tumour. Here, we report the whole-exome sequencing of a unique series of resected HCC tumours and matched recurrences. This cohort included patients who received a liver transplant and who were immunosuppressed at time of recurrence, in comparison to patients who underwent liver resection for HCC and immunocompetent at time of recurrence, therefore facilitating analyses of immune selection in driving evolutionary divergence. We find extensive evolutionary divergence between baseline and recurrent tumours, with the majority of mutations in our cohort being private, in the proce

SUBMITTER: Chakravarthy A 

PROVIDER: S-EPMC12359061 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature